Oxatomide after oral administration

The results obtained in the guinea-pig anaphylaxis test after oral oxatomide administration are presented in Fig. 1. A dose-dependent increase in the number of animals protected from the acute anaphylactic shock was observed and the histamine-induced paw oedema was similarly reduced by increasing doses of oxatomide. As previously found with cinnarizine, protection from anaphylactic shock was a more sensitive measure of the activity of oxatomide than was the reduction of paw oedema. In comparison with cinnarizine, however, oxatomide was considerably more potent. The calculated ED5o s, 2 h after oral administration, were 0. 16(0. 081 - 0. 31) mg/kg for protection from anaphylactic shock and 0. 30(0. 18 - 0. 50) mg/kg for inhibition of histamine oedema. 

Oxatomide has a relatively long duration of action. When challenged 6 h after oral administration of the compound, the guinea-pigs were protected from lethal anaphylaxis at about the same dose as found in the standard procedure. The calculated ED5Q for the 6 h-interval was 0. 14(0. 075 - 0. 28) mg g. Inhibition of the paw oedema induced by exogenous histamine in the same animals required a dose of 0. 56(0. 27 - 1.14) mg g. 

The individual intensities of PCA and histamine-induced reactions in rats after oral administration of oxatomide are presented in Fig. 2. A progressive dose-dependent inhibitory effect of oxatomide was obtained on both PCA and histamine reactions. 

Figure 3. Individual oedema indices for Ascaris coeloma fluid (ACF 1 100) and histamine reactions at various times after oral administration of oxatomide in the...

The median normal histamine concentration in the 30 control plasmas was 5. 0(4. 8 - 6. 1) ng/ml (confidence limits according to Owen, 44). Four hours after oral administration of oxatomide the median of the treated groups stayed within the control limits, except for the group treated with 10 mg g, in which the median plasma histamine concentration was 3. 0 ng/ml. 

Figure 1. Individual survival time and histamine oedema after oral oxatomide administration (t 2 hr) in the guinea pig anaphylaxis test...

In preliminary experiments oxatomide was administered at a relatively high dose of 10 mg/kg. This dose had no effect on gross behaviour of the animals, but virtually totally abolished the skin responses both to ACF (1 100) and to histamine (0. 5/ig), 4 h after its oral administration. 

In our experiments 30 adult Beagle dogs of either sex were used. Four hours after the oral administration of oxatomide or solvent 5 ml blood was sampled. This was followed by intravenous injection of Cremophor EL (BASF) 25 %, in a volume of 0. 1 ml/kg and further blood samples were collected 5, 15 and 30 min after the Cremophor injection. During this period behavioural changes were recorded. 

Figure 4. Histamine levels in the circulating blood of three dogs after iv injection of 0.1 mg/kg histamine in the control experiment (O) and 4 hr after the oral administration of 10 mg/kg oxatomide (0)...

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